Phenylethylamine (PEA) is an endogenous amine synthesized by decarboxylation of phenylalanine in dopaminergic neurons of the nigrostriatal system, and may act as a neuromodulator of catecholamine neurotransmission in the brain (1). The most important action of PEA is promoting the neurotransmission of catecholamines. It is known that PEA stimulates the release of acetylcholine as well as dopamine (2). Furthermore PEA increases norepinephrine neurotransmission (NE) (6) and even serotonin neurotransmission.
Recently it has been shown that PEA can also work as an autonomous neurotransmitter, with its specific neuronal receptors; and that it acts as a true neuromodulator, being also able to depress neurotransmission if needed. (8)
From this derive a whole series of effects: stimulation of attention and memory; mood enhancement, with significant antidepressant activity; promotion of empathy and thus sociality, included emotional and sexual behavior; inhibition of hunger; reduction of the need for substance abuse and drug dependency.
The link between PEA and emotional mood has been confirmed by studies whereby significantly lower levels of PEA, measured as such or through its metabolite PAA (phenylacetic acid) in the plasma or urines, have been found in depressed subjects. (9)
It has been seen that Parkinson's patients have significantly lower levels of PEA, as measured directly in the plasma (12). The progressive reduction of neurotransmission, particularly dopaminergic, in these patients, is related to the progressive degeneration of the dopaminergic neurons of the substantia nigra.
This reduction in the PEA levels goes together with a parallel increase in levels of MAO-B in parkinsonian patients, hence the drugs used in Parkinson's are MAO-B inhibitors such as selegiline. (14) Moreover, once ingested PEA can easily pass through the blood-brain barrier and stimulate the release of dopamine from the nigrostriatal tissue even at low dosages. This is an important distinctive character, because the drug currently used, selegiline, while inhibiting MAO-B and the reuptake of dopamine, does not have any action on its release from the nigrostriatal tissue, and so it does not help to produce more dopamine, a serious limit in a pathology such as Parkinson, where the very generation of dopamine is greatly jeopardized.
Alzheimer's disease involves a degeneration of the mechanism of production and reuptake of dopamine and the progressive destruction of the neurons of the striatal area, which over time brings to a low number of dopaminergic neurons, and consequently of dopamine transmission. (15)
Although there are no clear data on the fact that ADHD (Attention Deficit Hyperactivity Disorder) is a neurodegenerative pathology, some studies have tried to prove that neuronal destruction is a main cause of ADHD in both children and adults. (19)
Most importantly there are evidences whereby the children affected by ADHD and learning disabilities have significantly lower levels of PEA (21), and so a reduction in the neuromodulation of attention (dopamine) and sedation (serotonine). That is why the drug of choice for ADHD is methylphenidate, a synthetic derivative of PEA, which also acts by stimulating a higher production of PEA (22), and thus of dopamine and norepinephrine, two neurotransmitters directly involved in the etiology of ADHD.
It is well known the use of amphetamines to control hunger and, consequently, weight. Their use in this area has always been controversial due to their side effects which, given also their tolerance, tend to become potentially very serious over time. This is confirmed by the fact that the main drugs currently used for hunger and weight control are amphetamine-like dopaminergic antidepressants, such as venlafaxine and buproprion. These molecules, as all amphetamines, are synthetic derivatives of PEA. The latter acts as a potent appetite suppressant insofar as its degradation by MAO-B enzymes is prevented.
Monoaminoxidase (MAO) A and B catalyze the degradation of neuroactive and vasoactive amines in the CNS and in peripheral tissues. MAO-B in particular, given its direct and indirect relevance to dopaminergic transmission, is involved in neurological disorders where dopamine is essential, such a depression and mood disorders, Parkinson and Alzheimer diseases. For this reason, MAO-B inhibitors are used in the treatment of such neurological disorders. (26)